Human articular cartilage is an avascular structure, which has a complex, layered and avascular tri-dimensional structure, with an extracellular matrix (ECM) made by a few highly specialized cells (chondrocytes) that typically divide very slowly. Articular cartilage exhibits a poor intrinsic healing ability due to structural and biologic characteristics, and when injured, it poses significant hurdles to repair strategies. Not only does the defect need to be repopulated with cells, but preferentially with hyaline-like cartilage.
Current cartilage treatment options can be divided into stimulation and replacement strategies. Stimulation techniques or strategies attempt to bring mesenchymal progenitors from the marrow to differentiate and repopulate the defect. Although these techniques have shown good short-term results, the repair tissue eventually fails due to the inferior structural and mechanical qualities of the resulting fibrocartilage. Replacement, on the other hand, tries to fill the defect with a native tissue obtained from nearby healthy locations. Long-term complications, donor site-associated morbidity, and the scarcity of replacement tissue are the major disadvantages of the autologous component of this technique.
New methods to stimulate mesenchymal stem cells and generate a more durable implant can be broadly divided into pre- and post-implantation strategies. In vitro optimization techniques (pre-implantation) involve the use of specific scaffold materials that promote cell survival and induce cell differentiation; growth factors to manipulate cell proliferation, differentiation, ECM production, and cellular hypertrophic terminal differentiation; adjusted culture conditions to mimic the native environment (use of flow stimulation in a bioreactor); and genetically engineered MSCs to express specific targets (ie, transforming growth factor-beta-1 and insulin-like growth factor-1). Scaffolds chosen for effective tissue engineering with respect to cartilage repair can be protein-based (collagen, fibrin, and gelatin), carbohydrate-based (hyaluronan, agarose, alginate, PLLA/PGA, and chitosan), or formed by hydrogels.
Effective tissue engineering has the potential to improve the quality of life of millions of patients and delay or even prevent future medical costs related to cartilage or bone regenerative procedures. Scaffolds possessing the functional and mechanical features resembling those within the human knee joint both during gait and at rest are in a great need. Creating scaffolds having the right mechanical compression, fluid-induced shear stress, and hydrostatic pressure is highly desirable to assist in stimulating the development of more robust cells for implantation.